The inflammatory cytokines tumor necrosis factor alpha and interleukin-1 beta stimulate phosphatidylcholine secretion in primary cultures of rat typeII pneumocytes

Tumor necrosis factor a and interleukin-1 beta increase surfactant secretio n in type II pneumocytes in a time- and dose-dependent manner. This stimula tory effect was additive to that of lipopolysaccharide, suggesting that cyt okines and lipopolysaccharide may exert their actions through different sig nal transduction pathways. Tumor necrosis factor a and interleukin-1 beta d id not modify the increase on phosphatidylcholine secretion induced by the direct protein kinase C activator tetradecanoylphorbol 13-acetate, whereas this effect was inhibited by the protein kinase C inhibitors bisindolylmale imide (2 x 10(-6)M) and 1-(5-isoquinolinylsulphonyl)-2-methyl piperazone (1 0(-4)M). In addition, the stimulatory effect of tumor necrosis factor a and interleukin-1 beta was not suppressed by the intracellular Ca2+ chelator B APTA (5 x 10(-6)M) or by KN-62 (3 x 10(-5)M), a specific inhibitor of Ca2+- calmodulin-dependent protein kinase. These results suggest that tumor necro sis factor a or interleukin-1 beta stimulate phosphatidylcholine secretion via protein kinase C activation in a Ca2+-independent manner.